lymphoma radvax lymphoma: a phase ii trial of nivolumab + low dose radiotherapy for incomplete responders

Conditions: Hodgkin Lymphoma

Summary: this is a phase ii single-arm, single-site, open label clinical trial with r/r hl patients, aimed to determine whether a radvax approach using low-dose rt added to nivolumab can improve response among patients who do not achieve a cr to nivolumab alone. the long-term goal is to develop an effective regimen for r/r hl patients.

nivolumab 3 mg/kg will be administered on day 1 (pre-response assessment week 0) and on day 1 and continued per standard of care and institutional practices. at the week 1 biomarker collection, research fdg pet/ct will be performed to assess for fdg "flare." at week 8-12, pet/ct will be performed for the first response assessment. if a complete anatomic response is seen, nivolumab monotherapy will be continued on day 1 and continued per standard of care and institutional practices. by contrast, if at week 8 less than a complete anatomic response is seen, radiotherapy to 4 gy x 2 fractions will be administered (post-response assessment week 0). the patient will be evaluated by a radiation oncologist while on treatment, and toxicities will be recorded. nivolumab will be continued on day 1 and continued per standard of care and institutional practices. in either scenario, a second response assessment will be conducted \~8-12 weeks after the first response assessment. in either scenario, nivolumab monotherapy will be continued at the discretion of the treating medical oncologist. if there is less than cr post-rt and there is an additional untreated non-target lesion that can be followed, radiotherapy can again be administered when disease progresses to a previously untreated lesion, after which the patient will continue on the post-rt follow-up algorithm.

Eligibility criteria:
inclusion criteria: * pathologically confirmed hodgkin lymphoma for whom nivolumab is clinically indicated. * relapsed/refractory disease. * ≥2 sites of measurable disease, at least one outside of intended rt fields. * age ≥ 18 years. * ecog performance status of 0-2. * standard laboratory criteria for hematologic, and biochemical, and urinary indices within a range that, in the opinion of the physician, clinically supports enrollment of the subject on the trial. * patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial. * ability to provide written informed consent. exclusion criteria: * subjects with contraindications to immune checkpoint therapy, as follows: * interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. * prior organ allograft or allogeneic bone marrow transplantation. * subjects with contraindications to immune checkpoint therapy, as follows: * interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity. * prior organ allograft or allogeneic bone marrow transplantation. * pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication. * active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator. * condition requiring systemic treatment with either corticosteroids. * systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. steroids as anti-emetics for chemotherapy are strongly discouraged * intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted. * pregnant women, women planning to become pregnant and women that are nursing.